Antioxidants for Intrauterine Growth-restricted Newborns May Prevent Obesity and Diabetes

A recent study has revealed new hope for the potential treatment of intrauterine growth restricted newborns using the red grape antioxidant Resveratrol, to prevent future metabolic syndrome-related diseases such as obesity and diabetes.

Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is the second leading cause of perinatal morbidity and mortality and occurs in approximately 5% of the population. IUGR is the failure of a fetus with an estimated gestational weight below the 10th-percentile to thrive while in the womb. At birth, the cutoff weight for diagnosing an infant with IUGR is 5 pounds, 8 ounces.

Fetal growth is dependent upon a healthy uterine environment. When the uterine environment is suboptimal or compromised in some way, then fetal intrauterine growth restriction can occur. IUGR has many potential causes. Some causes include low oxygen conditions in the womb, an abnormal placenta, maternal diabetes, cardiovascular heart disease, hypertension, smoking, drinking and exposure to viruses including measles. The specter of the resurgence of measles is of particular concern for fetuses and newborns as noted in recent reports of measles outbreaks in the U.S.

In an earlier rat study published in the journal Diabetes, University of Alberta medical researchers Jason Dyck and Sandra Davidge discovered that feeding intrauterine growth restricted pups a diet high in fat resulted in increased fat deposits in the IUGR pups’ abdomens and the development of glucose intolerance and insulin resistance early in their adult lives. According to Dyck, "There is a concept that in utero, there are genetic shifts that are occurring—reprogramming is occurring because of this strenuous environment babies are in, that allows them to recover very quickly after birth," says Dyck. "When babies are growth-restricted, they usually have a catch-up period after they are born where they catch up to non-growth-restricted groups. It might be that reprogramming that creates this kind of 'thrifty' phenotype, where they want to consume and store and get caught up. That reprogramming appears to make them more vulnerable to developing a host of metabolic problems.”

Resveratrol - The Red Grape antioxidant
Resveratrol is popularly known as the Red Grape antioxidant due to an observation that the French - in spite of a diet high in fat and cholesterol - were among the list of nations with decreased incidences of heart disease. Initial theories abounded including the popular belief that antioxidants from red grapes in wine were responsible for the decrease in heart disease in France. Subsequent studies showed that the concentration of resveratrol in red wine was too low to account for any significant therapeutic benefits.

The researchers at the Faculty of Medicine & Dentistry at the University of Alberta report that low-oxygen conditions in the womb typically results in intrauterine growth restriction that increases a fetuses susceptibility to metabolic syndrome in the future as an adult. Due to previous studies indicating that the antioxidant resveratrol has insulin-benefiting properties in diabetics, they decided to test the postnatal effects a resveratrol supplement would have on an IUGR rat.

The design of the study was to create a compromised uterine environment by exposing pregnant rats to both normal and low-oxygen conditions during the last third of gestation. The control rats were placed under normal (21%) oxygen level conditions whereas the test rats were placed under relatively hypoxic (11.5%) oxygen level conditions.

After the birth of the pups, male offspring were randomly selected from both groups and fed for nine weeks either a high-fat diet alone, or a high-fat diet with a resveratrol antioxidant supplement.

The result of the experiment showed that IUGR rat offspring developed metabolic syndrome that included glucose intolerance and insulin resistance with increased abdominal fat deposits. However, only the IUGR offspring that were fed the resveratrol supplement with their high-fat diet had significantly reduced abdominal fat deposits as well as improved glucose intolerance and insulin resistance. The researchers concluded that their results suggest that early, postnatal administration of resveratrol can improve the metabolic status of high-fat fed rat IUGR offspring born from pregnancies complicated by low-oxygen conditions.

Future studies by the researchers will address whether treating the mother of IUGR pups during gestation can result in preventing metabolic syndrome from occurring in the pups after birth later in development.